The development of modern genomics and proteomics has created an opportunity for the development of rational peptide-based cancer therapeutics. Using plant-biomass production systems, it is now possible to generate therapeutic peptides and proteins quite inexpensively and in large quantities. The overall goal of this proposal is to develop peptide-based cancer therapeutics which can be produced by plant biomass, particularly tobacco. In collaboration with Large Scale Biology, Inc., scientists at the James Graham Brown Cancer Center have developed the ability to express peptides and proteins in tobacco plants. The Large Scale Biology processing plant at Owensboro, Kentucky has the capability of GMP production of tobacco-based therapeutics. This proposal will take advantage of the Brown Cancer Center expertise in cancer drug and vaccine development and the Large Scale Biology expertise in plant molecular biology and expression technology to accomplish the following specific aims: 1. To identify growth inhibitory peptide aptamers targeted to nucleolin and alpha-enolase, two cellular proteins expressed on the surface of cancer cells. 2. To develop effective human papillomavirus vaccines that can be produced in tobacco. The unique and complementary experience of Dr. Miller in aptamer development and Dr. Jenson in vaccine creation will ensure the success of this project. The accomplishment of these goals will have the duel advantage for Kentucky of developing new compounds with therapeutic potential and generating revenue for farmers who participate in the program. The development of a viable agripharmaceutical industry in the state will have additional benefits. The experiments which are proposed in this grant will allow Brown Cancer Center scientists to translate their laboratory observations into early phase clinical trials.